Although advances have been made in defining the genetics and antigenic properties of cellular antigens which behave as histocompatibility antigens, little information is yet available on the physical association of these antigens or their relation to the intrastructure of cell membranes. The topographic relation of the isoantigens specified by complex loci such as the H-2 in mouse and HL-A system in man is not known; nor is it known whether the molecular support which bears these entities represents only histocompatibility antigens. The initial objective of this investigation is to define the spatial and physical relation of H-2 isoantigens specified by the same and different crossover regions at the ultrastructural level employing the techniques of immuno-electronmicroscopy. The second objective is to explore the surface interaction of H-2 antigens using antibodies labeled with ferritin, hemocyanin, or southern bean mosaic virus. These studies will be of immediate importance to studies concerned with the isolation and physical characterization of histocompatibility antigens and, more broadly, to the study of membrane structure and function.